Uncovering the anticancer potential of nutraceuticals in colorectal polyp and cancer by integrating spatial transcriptomics and single cell RNASeq

Colorectal cancer (CRC) is the leading cause of gastrointestinal cancer-related deaths and the third most frequent disease globally in both men and women. According to several studies, edible medicinal plants such as cruciferous vegetables have been reported to play a key role in colorectal cancer prevention, partly because their bioactive compounds can counteract adverse components of the nutritional exposome associated with CRC risk. We integrated bulk-RNASeq, single cell RNASeq and spatial transcriptomics approaches to profile 354 colorectal cancer tissue samples. Multiple types of cells were determined utilizing the Seurat, SingleR, Celldex and SingleCellExperiment packages. CellChat discovered ligand-receptor communications, while monocle2 determined the development of the branching trajectory. GraphST and SpacexR packages was utilized for spatial transcriptomics analysis. Finally, we performed molecular docking for major nutraceutical compounds using AutoDock4. This is the first single cell spatial transcriptomic insight showing a significant reduction of epithelial cells (normal: 63.52% vs. polyp: 41.12%) and a notable increase of neutrophils (normal: 10.08% vs. polyp: 13.12%) in polyp tissues, while epithelial cells increased in polyp tissue (tumor: 76.19% vs. polyp: 84.08%). AICDA, CXCL12, and CMA1 were discovered to be crucial genes through spatial gene expression evaluation, and pseudotime trajectory assessment revealed that they played a role in initiating phenotypic changes that led to tumor-like cell states. Molecular docking demonstrated that dietary bioactive compounds, including cyanidin, glucotropaeolin, and pelargonidin, have strong binding affinities with these targets. In immunotherapy-focused approaches, these interactions revealed the potential capacities of nutraceutical compounds such as anthocyanidins and glucosinolates, especially in modulating the tumor microenvironment during both in the initial and advanced stages of colorectal cancer, highlights the role of dietary exposome in colorectal cancer prevention.